Prognostic value of a T-cell-based, interferon-gamma biomarker in children with tuberculosis contact.
BACKGROUND
Enzyme-linked immunospot (ELISpot) assay is an increasingly widely used, T-cell-based, interferon-gamma-release assay for diagnosing tuberculosis infection, but whether positive results are prognostic of active tuberculosis is not known.


OBJECTIVE
To determine whether ELISpot results predict the development of active tuberculosis among persons with recent tuberculosis exposure.


METHODS
Longitudinal cohort study of children and adolescents with tuberculosis contact recruited from October 2002 to April 2004.


METHODS
Community-based contact investigations in Turkey.


METHODS
908 children and adolescents with recent household tuberculosis exposure.


METHODS
Enzyme-linked immunospot assay, incorporating early secretory antigenic target-6 and culture filtrate protein-10, and tuberculin skin test were done at baseline.


METHODS
Incidence rates ratios of progression to active tuberculosis for contacts with positive tuberculin skin test and ELISpot results, and relative incidence rates comparing contacts with positive and negative test results.


RESULTS
Isoniazid preventive therapy was given to 688 (76%) contacts according to local guidelines. Fifteen contacts developed active tuberculosis over 1201 person-years of follow-up. Of 381 contacts with positive ELISpot results, 11 developed active tuberculosis over 536 person-years of follow-up (incidence rate, 21 per 1000 person-years [95% CI, 10.2 to 36.7 per 1000 person-years]), a statistically significant 3- to 4-fold increased risk for progression relative to ELISpot-negative contacts. Of 550 contacts with positive tuberculin skin test results, 12 developed active tuberculosis over 722 person-years of follow-up (incidence rate, 17 per 1000 person-years [CI, 8.6 to 29.0 per 1000 person-years]).


CONCLUSIONS
Only 3 of the 15 incident cases were confirmed by culture.


CONCLUSIONS
Positive ELISpot results predict subsequent development of active tuberculosis in recent tuberculosis contacts. Although tuberculosis contacts with positive ELISpot results have an incidence rate of tuberculosis similar to that of contacts with positive tuberculin skin test results, ELISpot testing could allow more focused targeting of preventive therapy to fewer contacts.
Bakir
Mustafa
M
Marmara University School of Medicine, Istanbul, Turkey.
Millington
Kerry A
KA
Soysal
Ahmet
A
Deeks
Jonathan J
JJ
Efee
Serpil
S
Aslan
Yasemin
Y
Dosanjh
Davinder P S
DP
Lalvani
Ajit
A
D000293:Adolescent; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016358:Contact Tracing; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism*; D007538:Isoniazid / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D012307:Risk Factors; D013601:T-Lymphocytes / Q000378:metabolism*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000517:prevention & control; D014421:Turkey / Q000453:epidemiology
D000995:Antitubercular Agents; D015415:Biomarkers; D007371:Interferon-gamma; D007538:Isoniazid